Topic 5 Disorders Of The Immune System

Front 1

What causes autoimmune diseases?

Back 1

First understand that clonal deletion ensures that most of the T and B cells that recognize your own cells are eliminated during their development in the thymus or the bone marrow
-The failure to eliminate self-reactive lymphocytes can cause autoimune diseases

Front 2

What are associated with autoimmune diseases?

Back 2

Depending on whether self-reactive T or B cells escape clonal deletion, these diseases are associated with either antibodies or T cells that attack and destroy the individuals own cells or tissues
-It is not known why self-reactive lymphocytes escape clonal deltion in some individuals

Front 3

What are examples of autoimmune diseaes?

Back 3

Autoimmune Hemolytic Anemia
-Myasthenia gravis

Front 4

Autoimmune Hemolytic Anemia - List causes and effects

Back 4

It is a disease in which people make antibodies against their own red blood cells
-Complement proteins lyse the antibody coated RBCs
-If there are too few RBCs your tissues won't receive enough oxygen

Front 5

Myasthenia gravis - List causes and effects

Back 5

It is a disease in which people make antibodies that bind the acteylcholine receptor on their muscle cells
-These antibodies block the receptor and prevent the muscle cells from responding to neutrotransmitters (acteylcholine) released by the nerve cells
-Acetycholine causes muscle cells to contract so if an antibody blocks the acteylcholine receptor, it could result in paralysis

Front 6

Antigen antibody complexes form large precipitates in the kidneys and causes blockages, how do we treat that?

Back 6

These diseases are often treated with steroid hormones that suppress the immune system (eg cortisone)

Front 7

Can Self-reactive Th1 cells cause autoimmune diseaes, if so how?

Back 7

Yes.
These Th1 cells recognize self antigens become activated and then secrete cytokines that cause an inflammatory response similar to a delayed type hypersensitivty response
-Activated macrophages infilitrate the tissue containing the self-antigen and release proteases and other substances that damage the tissue
-in one type of diabetes, the insulin producing cells in the pancrease are destroyed in this way

Front 8

What are immunodeficiency diseases?

Back 8

People whose immune system does not function properly may have difficulty eliminating pathogens
-People with mild immunodeficiency diseases may suffer from recurrent infections
-People with severe immunodeficienc diseases generally die of infections at an early age
-Severity of the disease is determineed by how much the immune system is defective

Front 9

What are examples of inherited immunodeficiency diseases?

Back 9

SCID (Severe combined immunodeficiency)

Front 10

What is SCID and what causes it

Back 10

It is a disease in which person has no functional T cells or B cells
-Several different mutations can cause this
-IN one type of SCID, enzymes that rearrange the gene segments that make up the immunoglobulin and T cell receptor genes are defective
-Resulting lymphocytes would have no mIg or TCRs and would not be able to detect the presence of pathogens
-In fact such useless lymphoctes fail to develop at all

Front 11

What are some effects due to defects in specific classes of immunoglobulin

Back 11

Failure to make IgG results in recurrent bacterial infections
-Failure to make IgA results in recurrent infections

Front 12

Deficiency in certain complement proteins result in what?

Back 12

-Recurrent bacteria infections
-Complement can directly lyse some types of bacteria
-IgM and IgG antibodies that have bound to the surface of bacterium can also activate complement resulting in lysis of bacterium
-Complement can also act as opsonins
-Complement proteins that have bound to surface of bacterium can be bound by a receptor on macrophage which allows for the macrophage to more efficiently phagocytose the bacterium

Front 13

What is AIDs?

Back 13

It is an immunodeficiency disease that is not inherited. (Aquired immunodeficiency)
-Causes the destruction of a persons helper T cells by the HIV

Front 14

What causes AIDS

Back 14

HIV causes aids
-HIV is a virus transmitted by contact with fluids (semen or blood) from an infected individual
-No airborne transmission

Front 15

What damage does AIDS do (mechanism behind aids)?

Back 15

HIV infects macrophages then spreads to helper T cells (CD4 T cells)
-Exposure to HIV results in production of antibodies to HIV
-This can be used as test for exposure to HIV, however antibodies provide little protection against disease because the virus resides inside the infected cells
-Virus can remain dormant (inactive) inside cells for long peroids of time (known as latency)
-Person can be HIV positive but healthy for long periods of time

Front 16

What activates HIV?

Back 16

When T cells or macrophages are activated during an infection, the virus wakes up and begins to replicate
-New viruses spread to other helper T cells and the infected helper T cells fuse together and die
-Loss of helper T cells causes AIDS
-Staying helathy and avoiding infection can prevent HIV from getting activated and can prevent progression to AIDS

Front 17

Why does a lack of CD4-T cells cause aids?

Back 17

With no helper T cells, B cells can't make antibodies, macrophages can't kill intracellular bacteria and CTL-P cannot be fully activated to kill virally infected cells
-People with AIDs get bacterial infections and usually die from opportunistic infections which healthy people can easily eliminate
-Common cause of death is pneumonia

Front 18

How can we monitor the development of a person into full blown AIDS from being HIV positive?

Back 18

By monitoring the number of helper T cells in the blood, doctors can monitor the progression from being HIV positive to having full blown AIDS
-Clinical definition of AIDS is a T helper cell count that is <20% of the normal level

Front 19

How do we prevent a treat AIDS?

Back 19

Best way of doing so is to avoid high-risk activities

If we do get aids and become HIV-positive, staying helathy can keep the virus dormant
-Person can be HIV positive for many years and remain healthy but if T cells and macrophages that are infected with HIV become activated during an immune response the virus is reactived and when this happens new HIV viruses are made which then spread to other cells and cause AIDS

Front 20

Is it possible to make a vaccine that will prevent infection by HIV?

Back 20

Let's consider this
-HIV entry into cells requires that HIV gp120 protein bind to proteins on the surface of macrophages and T cells
-A vaccine that stimulated the production of antibodies directed against gp120 could neutralize the virus and prevent it from entering cells
-Vaccine could consist of inactived HIV, a related virus that does not fcause disease in humans but expresses a protein similar to HIV gp120 protein a harmless virus engineered to express the HIV gp120 protein on its surface or purified HIV gp120 protein
-But HIV mutates rapidly
-Antibodies induced by the vaccine could protect against the HIV strain used to make the vaccine but would not protect against new strains with altered gp120, thus so far vaccines are not a vaible alternative

Front 21

What is the aim for current treatments to counteract aids?

Back 21

The aim is to limit the spread of the HIV virus by interfering with its ability to replicate or to infect new cells

Front 22

So what is one method of treating aids?

Back 22

Inhibiting the enzymes (reverse transcriptase) that is responsible for copying the genetic material of the virus can block HIV replication
-Drugs that do this are AZT and ddl
-Both prevent reverse transcriptase from making complete DNA copies of the HIV genome

Front 23

What is a treatment to prevent the formation of infectious virus particles?

Back 23

When new HIV viruses are made, one of the proteins has to be cut into two parts by a viral protease enzyme in order for the virus to be able to infect other cells
-An inhibitor of the protease has been developed which seems to be effective at stopping the spread of the virus

Front 24

What is the current method of treating against aids?

Back 24

A combination of AZT, ddl, and protease inhibotrs
-However, despite intial promising results effectiveness of these drugs appears to be declining, perhaps the HIV virus has mutated to become more resistant to these drugs

Front 25

What was the 1996 breakthrough in understanding how HIV viruses enter cells?

Back 25

-Suggests a new way to limit spread of HIV in infected persons
-HIV entry into macrophages requirs binding of HIV gp120 protein to CD4 (low levels of CD4 on human macrophages) and to a second receptor on macrophages called CCR5
-HIV entry into T cells requires binding of HIV gp120 protein to CD4 and to a second receptor on T cells called CXCR4
-Not partical to block CD4 by injecting people with antibodies to CD4
-CD4 is required for helper T cells to bind to peptide/MHC class II complexes, antibodies to CD4 would intefere with the function of helper T cells and in fact create a situation much like AIDS

Front 26

What are CCR5 and CXCR4?

Back 26

They are receptors for a class of cytokines called chemokines
-There are many chemokine receptors, some of which have overlapping functions, (bind the same chemokines) thus any one chemokine recpetor may not be essential

Front 27

What is so special about people who have defective CCR5

Back 27

They are healthy and appear to be resistant to HIV infection

Front 28

So with the recent developments whats a strategy to prevent hte spread of HIV ?

Back 28

Block CCR5 and CXCR4 by injecting altered versions of chemokines.
By binding to CCR5 and CXCR4 these altered chemokines would prevent HIV from binding to these receptors and then entering the cell
-Chemokines will need to be altereed so that they still bind to their receptors but do not perform their usual function (cause inflammation)
-If altered chemokines can limit the spread of HIV infection then the persons CTLs may have a chance to kill the HIV infected cells and eliminate the infection